Arias-Aragón, FranciscoTristán Clavijo, EnriquetaMartínez Gallego, IreneRobles Lanuza, EstefaníaCoatl-Cuaya, HeribertoMartín-Cuevas, CeliaSánchez Hidalgo, Ana CarmenRodríguez Moreno, AntonioMartínez Mir, AmaliaGómez Scholl, Francisco Manuel2024-07-302024-07-302023-05-13Arias-Aragón, F., Tristán Clavijo, E., Martínez Gallego, I., Robles Lanuza, E., Coatl-Cuaya, H., Martín-Cuevas, C.,...,Gómez Scholl, F.M. (2023). A Neuroligin-1 mutation associated with Alzheimer’s disease produces memory and age-dependent impairments in hippocampal plasticity. iScience, 26 (6), 106868. https://doi.org/10.1016/j.isci.2023.106868.2589-0042https://hdl.handle.net/11441/161756Alzheimer’s disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.application/pdf24 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1016/j.isci.2023.106868